Fluorescent ligands for dopamine D/D receptors.

Sci Rep

Department of Chemistry and Pharmacy, Medicinal Chemistry, Friedrich-Alexander-Universität Erlangen-Nürnberg, Nikolaus-Fiebiger-Str. 10, 91058, Erlangen, Germany.

Published: December 2020

AI Article Synopsis

  • Fluorescent ligands are crucial for studying G protein-coupled receptors and are applicable in various assays like FRET and BRET.
  • The research developed dansyl-labeled ligands for dopamine D-like receptors, which are important for treating neurological disorders like Parkinson's and schizophrenia.
  • These ligands demonstrated high binding affinities and effectiveness in different fluorescent applications, showcasing potential for real-time visualization in living cells.

Article Abstract

Fluorescent ligands are versatile tools for the study of G protein-coupled receptors. Depending on the fluorophore, they can be used for a range of different applications, including fluorescence microscopy and bioluminescence or fluorescence resonance energy transfer (BRET or FRET) assays. Starting from phenylpiperazines and indanylamines, privileged scaffolds for dopamine D-like receptors, we developed dansyl-labeled fluorescent ligands that are well accommodated in the binding pockets of D and D receptors. These receptors are the target proteins for the therapy for several neurologic and psychiatric disorders, including Parkinson's disease and schizophrenia. The dansyl-labeled ligands exhibit binding affinities up to 0.44 nM and 0.29 nM at DR and DR, respectively. When the dansyl label was exchanged for sterically more demanding xanthene or cyanine dyes, fluorescent ligands 10a-c retained excellent binding properties and, as expected from their indanylamine pharmacophore, acted as agonists at DR. While the Cy3B-labeled ligand 10b was used to visualize DR and DR on the surface of living cells by total internal reflection microscopy, ligand 10a comprising a rhodamine label showed excellent properties in a NanoBRET binding assay at DR.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736868PMC
http://dx.doi.org/10.1038/s41598-020-78827-9DOI Listing

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